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Semi-synthesis method of abietane diterpene and derivative thereof, abietane diterpene derivative and application

A technology of rosinane diterpene and synthesis method, applied to semi-synthesis of rosinane diterpenes and derivatives thereof, rosin alkane diterpenes derivatives and application fields, can solve the problem of excessive time consumption, low nepetaefolin and limited biological activity In-depth research and other issues to achieve strong anti-tumor activity and simple operation

Active Publication Date: 2021-06-08
SHANGHAI UNIV OF T C M
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004]However, the contents of triptobenzene L and nepetaefolin F in the above two species are extremely low, which limits the in-depth study of their biological activities. Preparation is a feasible way to solve this problem, but designing a total synthetic route starting from simple substrates is too time-consuming

Method used

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  • Semi-synthesis method of abietane diterpene and derivative thereof, abietane diterpene derivative and application
  • Semi-synthesis method of abietane diterpene and derivative thereof, abietane diterpene derivative and application
  • Semi-synthesis method of abietane diterpene and derivative thereof, abietane diterpene derivative and application

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Experimental program
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Effect test

Embodiment 1

[0042] The structural formula of the abietane diterpene of present embodiment 1 is as follows:

[0043]

[0044] The semi-synthetic method of this abietane diterpene comprises the following steps:

[0045] 1) Pour the raw material dehydroabietic acid 1-1 (25g, 83mmol) into an eggplant-shaped bottle, add magneton and solvent toluene 125ml, then add 15ml of ultra-dry pyridine, lead tetraacetate (74g, 207.5mmol), After heating and refluxing in an oil bath at 120°C for 2 hours, the conversion of the raw materials was complete, and the reaction system was filtered through diatomaceous earth to obtain a brown clear solution, and the toluene was spin-dried by an oil pump at 40°C. Then perform silica gel column chromatography, PE can elute the product, and the three products cannot be separated, and the hydrogen nuclear magnetic spectrum shows that the ratio of the three products obtained by the reaction is about 3:3:2. After concentration, the colorless oil 2-1-2-3 (21.4 g) was o...

Embodiment 2

[0054] The structural formula of the abietane diterpene derivative of present embodiment 2 is as follows:

[0055]

[0056] Take a dry eggplant-shaped flask, add substrate 1 (40 mg, 0.133 mmol), and replace the argon gas 3 times. Under the protection of argon, the above compound was dissolved in anhydrous dichloromethane (2ml), and DMAP (1.7mg, 0.0133mmol) and pyridine (21.4μl, 0.266mmol) were added successively, and acetic anhydride (13.7μl, 0.146mmol) was injected after reacting for 2min. mmol), overnight reaction. The next day, TLC showed that the raw material was still remaining, and there was a by-product protected by the 3-hydroxyacetyl group. NaHCO 3 The reaction was quenched with aqueous solution, extracted with ethyl acetate (4×2mL), the combined organic phases were washed with water, dried over anhydrous sodium sulfate, concentrated by filtration, and purified by flash column chromatography (PE / EA=5:1) to obtain a white solid, which Structural formula such as 2...

Embodiment 3

[0075] The structural formula of the abietane diterpene derivative of present embodiment 3 is as follows:

[0076]

[0077] Propionic acid was condensed with 20 mg of triptobenzene L (structural formula 1) to obtain the double-substituted product 9-1 and the mono-substituted product 19-cyclopropanecarboxyl-triptobenzene L (structural formula 3), respectively. After silica gel column chromatography, petroleum ether-ethyl acetate Gradient elution was carried out in the ester solvent system, and the derivatives of triptobenzene L were obtained by separation and purification, the structural formula of which was shown in 3.

[0078] The physical and chemical constants and hydrocarbon data of 19-cyclopropanecarboxyl-triptobenzene L:

[0079] white solid, 1 H NMR (400MHz, CDCl 3)δ7.16(d, J=8.2Hz, 1H), 7.00(dd, J=8.1, 2.1Hz, 1H), 6.89(d, J=2.0Hz, 1H), 4.45(d, J=11.7Hz, 1H), 4.23(d, J=11.7Hz, 1H), 3.35(dd, J=11.4, 4.9Hz, 1H), 2.94(dd, J=17.0, 6.1Hz, 1H), 2.83(overlapped, 2H), 2....

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Abstract

The invention relates to a semi-synthesis method of abietane diterpene and a derivative thereof, the abietane diterpene derivative and application. Dehydroabietic acid is taken as a raw material, dehydroabietic acid is subjected to six-step reaction such as decarboxylation, allylic oxidation, hydroboration oxidation and alkylation to obtain abietane diterpene triptobenz L, acetic anhydride and cyclopropanecarboxylic acid are respectively selected to be subjected to acetylation and condensation reaction with the abietane diterpene triptobenz L, and the nepetafolin F and a new compound 19-cyclopropanecarboxyl-triptobenz L are respectively generated. The semi-synthesis method provided by the invention is simple and safe to operate, a compound basis is provided for carrying out anti-tumor mechanism experiments, in-vivo pharmacological experiments and pharmacokinetics experiments of the compounds, and the synthesized new compound has a better anti-tumor effect.

Description

technical field [0001] The invention relates to the field of compounds, in particular to a semi-synthetic method of abietane diterpene and its derivatives, abietane diterpene derivatives and applications. Background technique [0002] Abietin compounds have always been one of the hotspots of plant chemists and organic synthetic chemists. The earliest research can be traced back to about the 19th century AD, when people obtained an acidic compound—abietic acid from rosin; in 1968, Japan Chemical Home Fujita synthesized abietane compounds by chemical method for the first time. In recent years, countless reports have been made on the chemical synthesis of abietane compounds. [0003] Two diterpene components, Triptobenzene L and nepetaefolin F, were isolated by our research group from Caryopteris nepetaefolia and C. aureoglandulosa, among which nepetaefolin F is a new compound with a typical abietane-type diterpene carbon Skeleton structure, C epoxidation dehydrogenation to f...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C29/14C07C35/42C07C69/16C07C67/08C07C69/743A61K31/22A61K31/215A61P35/00
CPCC07C29/14C07C67/08A61K31/22A61K31/215A61P35/00C07C35/42C07C69/16C07C69/743Y02P20/55
Inventor 侴桂新王永丽毛旭东杜婷婷
Owner SHANGHAI UNIV OF T C M
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